Microparticulate systems that utilize one or more polymers are widely used for biomedical applications such as drug delivery, bio-analysis, and clinical diagnosis. However, the particles produced by conventional manufacturing methods are typically limited to a spherical shape, relatively wide size distributions, and symmetrical monolithic or core-shell structures. While spherical microparticles are useful for certain applications such as drug delivery, non-spherical particles may have more desirable characteristics. For example, discrete control of particle geometry may facilitate more precise bio-analysis and controlled drug delivery because the shape of a particle can be tailored to function more effectively under certain predefined conditions. Thus, there is a need for a method for fabricating microparticles in a variety of three-dimensional shapes and geometric configurations.
Microfabrication techniques conventionally used for making integrated circuits have been utilized to create microparticles by combining silicon dioxide or polymethylmethacrylate (PMMA) and a photo-sensitive polymer. These techniques can be used to create microparticles having a precise shape, uniform size and specifically designed structures and surface chemistries, thereby making them suitable for use as drug-carrying vehicles. However, these techniques are limited in that they (i) require the use of photolithography to create every particle and (ii) are compatible with only certain materials. Moreover, the rigorous conditions, including highly aggressive solutions and elevated temperatures, which are used to release fabricated microparticles into solution may damage fragile compounds that have been incorporated into the microparticles. Thus, there are significant limitations to using known photolithographic techniques for microfabrication of microparticles.
An alternative to conventional photolithographic techniques is soft-lithography. Soft lithography is a collective term that refers to a group of non-photolithographic microfabrication techniques that employ elastomeric stamps having certain three dimensional relief features to generate micro-structures and even nano-structures. A more detailed description of soft lithography is found in Xia and Whitesides, Annual Review of Materials Science 28: 153-84 (1998) incorporated herein by reference. Thus, there is a need to utilize alternate microfabrication techniques such as soft lithography to create polymer microparticles having certain desired geometries.